A budget is requested to assemble state-of-the-art combined liquid chromatograph mass spectrometer under computer control. This system will incorporate the thermospray interface developed by Marvin Vestal in which samples are ionized in solution by chemical processes and ejected from droplets following the principles delineated by J. V. Iribarne. Apart from the obvious advantages of the mass spectrometer as a universal, yet highly specific, detector for liquid chromatography, this novel ionization method appears to offer unique potential for analysis of multiply charged species, involatile and polar samples. Four major users propose to develop and exploit this analytical capability for glucuronides, for metabolites of cyclophosphamide and cyclosporin, and for analysis of oligosaccharides and glycopeptides from glycoproteins. Six additional projects are described as examples of other potential users in the environment. These address analysis of gangliosides, phospholipids, steroidal suicide substrates, phosphonoformate, and glycopeptides, and studies of the mechanism(s) of ionization in the thermospray device aimed at improving analytical utility. HPLC is already being used in all of the analytical projects described, in some cases off-line with mass spectrometry. Major benefits will be realized from the combined instrumental system for analytes which are not UV chromophores, which are unstable to extended manipulation, and which are present at low levels in complex mixtures. The system proposed will handle samples weighing up to 1800 atomic mass units. A research associate is available to take responsibility for the instrument, who has training and considerable experience in operating and maintaining a thermospray LCMS-computer system.